The insulin-like growth factors (IGFs) constitute a family of proteins having insulin-like and growth stimulating properties. The IGFs show close structural homology with proinsulin and elicit similar biological effects. The IGFs are circulating, mitogenic peptide hormones that have an important role in stimulating growth, differentiation, metabolism and regeneration both in vitro and in vivo.
IGF-I action can be essential for the regulation of tissue formation and remodeling, bone growth, prenatal growth, brain development, and muscle metabolism. Cellular effects of IGF-I are mediated through the IGF-I receptor, a transmembrane tyrosine kinase that phosphorylates intracellular substrates, resulting in the activation of multiple intracellular signaling cascades.
IGF-I can play a critical role in the growth and development of many tissues in the body. It is a key regulator of skeletal muscle development, and continues to enhance the ability for muscle to grow and undergo repair throughout life. In skeletal muscle, IGF-I coordinates with additional growth factors to promote myoblast proliferation, differentiation, and fiber formation during normal growth as well as during regeneration after injury. Increasing IGF-I levels can result in functional hypertrophy in young adult animals, maintenance of mass and regenerative capacity in senescent animals, and enhancement of muscle recovery to counter acute and chronic damage.
Thus, IGF-I can be a central therapeutic target for enhancing muscle function in aging and disease. Several strategies have been employed to boost IGF-I levels in muscle, including tissue-specific transgenic expression (1-3), viral-mediated gene transfer (4-8), and directed recombinant IGF-I delivery (7, 8). However, more effective techniques for increasing IGF-I levels are needed.